Current studies include a double-blind randomized placebo add-on controlled trial of felbamate. The unique three period cross-over design allows unbiased estimates of drug effects even in the presence of a carry-over effect from one period to the next. The first study has been completed, and the results suggest the drug may be effective against partial seizures. A study of felbamate monotherapy is planned, as well as an add-on to valproic acid in the Lennox-Gastaut syndrome. We are studying carbamazepine withdrawal, to establish the presence or absence of transient seizure exacerbation. We have evaluated the effect of valproic acid on cerebral glucose metabolism, using positron emission tomography (PET). This drug is of particular interest due to its possible inhibition of GABA degradative enzymes. We compared its effect to that of phenytoin, carbamazepine, and phenobarbital. Valproic acid reduced cerebral metabolism by 20%, suggesting an interaction with the GABA-benzodiazepine receptor complex. PET is also being used to study the opiate receptor system in patients with epilepsy. 18F-cyclofoxy binding was assessed in patients with complex partial seizures, and naloxone administered to study its effect on blood flow and metabolism.